Journal Article

FZJ-2023-01361

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png One-shot 13 C15 N-metabolic flux analysis for simultaneous quantification of carbon and nitrogen flux.

Borah Slater, K. ; Beyß, M.FZJ* ; Xu, Y. ; Barber, J. ; Costa, C. ; Newcombe, J. ; Theorell, A.FZJ* ; Bailey, M. J. ; Beste, D. J. V. ; McFadden, J. ; Nöh, K. (Corresponding author)FZJ*

2023
EMBO Press Heidelberg

This record in other databases:      

Please use a persistent id in citations: http://hdl.handle.net/2128/34167  doi:10.15252/msb.202211099

Abstract: Metabolic flux is the final output of cellular regulation and has been extensively studied for carbon but much less is known about nitrogen, which is another important building block for living organisms. For the tuberculosis pathogen, this is particularly important in informing the development of effective drugs targeting the pathogen's metabolism. Here we performed 13 C15 N dual isotopic labeling of Mycobacterium bovis BCG steady state cultures, quantified intracellular carbon and nitrogen fluxes and inferred reaction bidirectionalities. This was achieved by model scope extension and refinement, implemented in a multi-atom transition model, within the statistical framework of Bayesian model averaging (BMA). Using BMA-based 13 C15 N-metabolic flux analysis, we jointly resolve carbon and nitrogen fluxes quantitatively. We provide the first nitrogen flux distributions for amino acid and nucleotide biosynthesis in mycobacteria and establish glutamate as the central node for nitrogen metabolism. We improved resolution of the notoriously elusive anaplerotic node in central carbon metabolism and revealed possible operation modes. Our study provides a powerful and statistically rigorous platform to simultaneously infer carbon and nitrogen metabolism in any biological system.

Keyword(s): Bayesian metabolic flux analysis ; Mycobacterium tuberculosis ; carbon metabolism ; isotope labeling ; nitrogen metabolism

---

Contributing Institute(s):

1. Biotechnologie (IBG-1)

Research Program(s):

1. 2171 - Biological and environmental resources for sustainable use (POF4-217) (POF4-217)

Appears in the scientific report 2023

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---